The (pro)renin receptor ((P)RR) is thought to enhance the activity of the tissue renin–angiotensin system by binding to renin or prorenin, and it can activate intracellular tyrosine-phosphorylation-dependent pathways independently of RAAS.236 However, whether (pro)renin/(P)RR contributes to hypertension in human is controversial. This evidence concerns the gene REN and hypertensive disorder.